Effects of probiotic supplementation on 12 min run performance, mood management, body composition and gut microbiota in amateur marathon runners: A double-blind controlled trial.

Background: Probiotic supplementation has a positive effect on endurance exercise performance and body composition in athletes, but the underlying mechanisms remain unclear. Gut microbiota can provide measurable markers of immune function in athletes, and microbial composition analysis may be sensitive enough to detect stress and metabolic disorders caused by exercise. Methods: Nineteen healthy active amateur marathon runners (15 male and 4 female) with a mean age of 29.11 years volunteered to participate in this double-blind controlled study. Based on the performance of the Cooper 12-min running test (CRT), the participants were allocated into two groups to receive either a probiotic formulation comprising lactobacillus acidophilus and bifidobacterium longum (n = 10) or placebo containing maltodextrin (n = 9) for five weeks. Consistency of diet and exercise was ensured throughout the experimental period. Before and after the intervention, all participants were assessed for CRT, emotional stability and gastrointestinal symptoms, gut microbiota composition, body composition and magnetic resonance imaging (MRI) indicators of skeletal muscle microcirculation. Results: Compared to before the intervention, the probiotics group showed an increase in CRT score (2.88 ± 0.57 vs 3.01 ± 0.60 km, P＜0.05), significant improvement in GSRS and GIQLI (9.20 ± 4.64 vs 7.40 ± 3.24, 118.90 ± 12.30 vs 127.50 ± 9.85, P＜0.05), while these indicators remained unchanged in the control group, with a significant time-group interaction effect on gastrointestinal symptoms. Additionally, some MRI metabolic cycling indicators of the thigh skeletal muscle also changed in the probiotics group (P＜0.05). Regarding microbiota abundance, the probiotics group exhibited a significant increase in the abundance of beneficial bacteria and a significant decrease in the abundance of harmful bacteria post-intervention (P＜0.05). Conclusion: As a sports nutritional supplement, probiotics have the potential to improve athletic performance by optimizing the balance of gut microbiota, alleviating gastrointestinal symptoms.

Comparison of haploidentical-allogeneic hematopoietic stem cell transplantation and intensive immunosuppressive therapy for patients with severe aplastic anemia with an absolute neutrophil count of zero: a retrospective study.

A retrospective analysis was conducted based on the clinical data from 60 patients older than 16 years from January 2016 to January 2021. All the patients were newly diagnosed with severe aplastic anemia (SAA) with an absolute neutrophil count (ANC) of zero. We compared the hematological response and survival of haploidentical-allogeneic hematopoietic stem cell transplantation (HID-HSCT) (n = 25) and intensive immunosuppressive therapy (IST) (n = 35) treatments. At six months, the overall response rate and complete response were significantly higher in the HID-HSCT group than those in the IST group (84.0% vs. 40.0%, P = 0.001; 80.0% vs. 17.1%, P = 0.001). With a median follow-up of 18.5 months (4.3~30.8 months), patients in the HID-HSCT group had longer overall survival and event-free survival (80.0% vs. 47.9%, P = 0.0419; 79.2% vs. 33.5%, P = 0.0048). These data suggested that HID-HSCT might be an effective alternative treatment option for adult patients with SAA with an ANC of zero, which requires further validation in an additional prospective study.

Epstein-Barr-virus-associated hepatitis with aplastic anemia: A case report.

BACKGROUND: Hepatitis-associated aplastic anemia (HAAA) is a rare condition. Patients with HAAA usually present with acute hepatitis, jaundice and significantly increased transaminase. After 1-2 mo, hepatitis gradually improves, but progressive hemocytopenia, bone marrow hematopoietic failure, and severe or extremely severe aplastic anemia are manifest. Most cases of HAAA are fulminant and usually lethal if left untreated. The literature on Epstein-Barr virus (EBV)-associated HAAA is sparse. CASE SUMMARY: We report a 30-year-old man who was admitted to our hospital because of pale yellow urine and skin with a simultaneous decrease in peripheral blood ternary cells. We made a diagnosis of EBV-associated HAAA. The treatment strategy for this patient included eltrombopag, an immunosuppressive regimen of rabbit anti-human thymocyte immunoglobulin, cyclosporine, and supportive care. The patient was discharged in normal physical condition after five months. A hemogram performed on follow-up revealed that he had achieved a complete response. CONCLUSION: Eltrombopag plus anti-thymocyte globubin and cyclosporine may be a therapeutic option for EBV-associated HAAA.Larger studies are warranted to confirm.

FN1 overexpression is correlated with unfavorable prognosis and immune infiltrates in breast cancer.

Objective: To investigate the correlation of fibronectin 1 (FN1) expression with prognosis and tumor-infiltrating immune cells in breast cancer (BRCA). Methods: FN1 mRNA and protein expressions were analyzed through Tumor Immune Estimation Resource (TIMER), Gene Set Cancer Analysis (GSCA), Human Protein Atlas (HPA) databases, and immunohistochemical analysis. The clinicopathological characteristics and genetic factors affecting the FN1 mRNA expression were assessed by various public databases. Then, we analyzed the prognostic value of FN1 in BRCA by Kaplan-Meier plotter, receiver operating characteristic, and Cox regression analyses. Further, the UCSC Xena database was used to retrieve TCGA-BRCA expression profiles for functional enrichment analysis and immune cell infiltration analysis. The potential drugs for the BRCA patients with high- FN1 expression were identified using the connectivity map analysis. Results: FN1 was upregulated in BRCA tissues compared with normal tissues. High FN1 mRNA expression was correlated with poor clinical outcomes and had good performance in predicting the survival status of BRCA patients. Further, Cox regression analysis showed that FN1 was an independent prognostic factor for predicting the overall survival of patients with BRCA. Moreover, hypermethylation of FN1 contributed to a better prognosis for BRCA patients. Functional enrichment analyses revealed the ECM-receptor interaction pathway and focal adhesion as the common pathways. Moreover, FN1 showed a significant association with tumor-infiltrating immune cells and immune checkpoint inhibitors. Several drugs such as telmisartan, malotilate, and seocalcitol may have therapeutic effects in BRCA patients with high FN1 expression. Conclusion: FN1 might serve as a novel prognostic biomarker and a novel therapeutic target for BRCA. Besides, the association of FN1 with immune cells and immune checkpoint inhibitors may provide assistance for BRCA treatment.

Design, synthesis, and biological evaluation of 3-(1-benzotriazole)-nor-ß-lapachones as NQO1-directed antitumor agents.

A series of novel 3-(1-benzotriazole)-nor-ß-lapachones 5a-5l were synthesized as the NQO1-targeted anticancer agents. Most of these compounds displayed good antiproliferative activity against the breast cancer MCF-7, lung cancer A549 and hepatocellular carcinoma HepG2 cells in agreements with their NQO1 activity. Among them, compound 5k was identified as a favorable NQO1 substrate. It could activate the ROS production in a NQO1-dependent manner, arrest tumor cell cycle at G0/G1 phase, promote tumor cell apoptosis, and decrease the mitochondrial membrane potential. In HepG2 xenograft models, 5k significantly suppressed the tumor growth with no influences on animal body weights. Therefore, 5k could be a good lead for further anticancer drug developments.

Design, synthesis, and biological evaluation of 4-substituted-3,4-dihydrobenzo[h]quinoline-2,5,6(1H)-triones as NQO1-directed antitumor agents.

A novel series of 4-substituted-3,4-dihydrobenzo[h]quinoline-2,5,6(1H)-triones as NQO1-directed antitumor agents were designed, synthesized, biologically evaluated. Compounds 3n, 3o and 3j proved to be good NQO1 substrates that showed increased metabolic rates relative to that of ß-lapachone. In addition, 3n, 3o and 3j potently inhibited the growth of NQO1-rich breast cancer MCF-7 cell, liver hepatocellular HepG2 cell, and lung cancer A549 cell. In cellular mechanistic studies, the representative compound 3o triggered ROS generation depending on the NQO1 dose, and induce HepG2 cell apoptosis by the generated oxidative stress. In HepG2 xenografts mouse model, at the dose of 20 mg/kg, 3o remarkably suppressed the tumor growth without affecting the animal weights.

Current Treatment Patterns of Aplastic Anemia in China: A Prospective Cohort Registry Study.

Aplastic anemia (AA) is a hematologic disease characterized by pancytopenia and hypocellular bone marrow, potentially leading to chronic anemia, hemorrhage, and infection. The China Aplastic Anemia Committee and British Committee for Standards in Haematology guidelines recommend hematopoietic stem-cell transplantation (HSCT) or immunosuppressive therapy (IST) comprising antithymocyte globulin (ATG) with cyclosporine (CsA) as initial treatment for AA patients. With limited epidemiological data on the clinical management of AA in Asia, a prospective cohort registry study involving 22 AA treatment centers in China was conducted to describe the disease characteristics of newly diagnosed AA patients and investigate real-world treatment patterns and patient outcomes. Of 340 AA patients, 72.9, 12.6, and 3.5% were receiving IST, traditional Chinese medicine, and HSCT, respectively, at baseline; only 22.2% of IST-treated patients received guideline-recommended ATG with CsA initially. Almost all patients received supportive care (95.6%) as blood transfusion (97.8%), antibiotics (63.7%), and/or hematopoietic growth factors (58.2%). Overall, 64.8% achieved a partial or complete response, and 0.9% experienced relapse. No new safety concerns were identified; serious adverse events were largely unrelated to the treatment regimen. These results demonstrate the need to identify and minimize treatment barriers to standardize and align AA management in China with treatment guideline recommendations and further improve patient outcomes.

Multiple risks analysis for aplastic anemia in Zhejiang, China: A case-control study.

To understand the risks associated with aplastic anemia (AA) in 4 cities of Zhejiang Province, China, with special focus on the joint contributions of multiple risks.Based on an Electronic Data Capture (EDC), a case control study was carried out. Data regarding socio-demographic, diseases history, living habits, and exposures to toxic substances, etc., were collected through survey questionnaires. t Test, chi-square test, or non-parametric rank sum test, and univariate and multivariate Logistic regression analysis were conducted to analyze data.The univariate logistic regression analysis results indicated that among all study participants (n = 1802), AA was associated with over 30 risks, in terms of their individual behaviors, daily and environmental exposures, diseases history, and family history. Multivariate logistic regression analysis further confirmed that the independent risks related to AA included presence of chemical factory within 3 km of living residence (odds ratio [OR] = 8.73, 95% CI: 1.42-53.74, P = .019), living in a newly decorated house/apartment (OR = 25.37, 95% CI: 4.44-144.81, P < .001), vegetarian diet (OR = 131.60, 95% CI: 3.45-5020.16, P = .009), preference of sugar (OR = 89.38, 95% CI: 7.22-1106.44, P < .001), preference of oily food (OR = 55.68, 95% CI: 5.12-605.26, P = .001), drinking lake water or pond water (OR = 58.05, 95% CI: 3.21-1049.81, P < .001), habit of staying up late (OR = 11.87, 95% CI: 3.43-41.02, P < .001), infection history (OR = 10.08, 95% CI: 2.75-36.93, P < .001). Result of receiver operating characteristic curve (ROC) analysis on the joint contribution of multiple risks indicated that AA was 13.835 times likely to occur when exposed to ≥1 risks than those exposed to 0 risks (95% CI: 9.995-19.149).Our study results demonstrated a comprehensive epidemiological pattern, in which the joint contributions of individual inherited health status, environment exposure, and individual behaviors lead to the occurrence of AA.

A newly identified cluster of glutathione S-transferase genes provides Verticillium wilt resistance in cotton.

As the largest cultivated fiber crop in the world, cotton (Gossypium hirsutum) is often exposed to various biotic stresses during its growth periods. Verticillium wilt caused by Verticillium dahliae is a severe disease in cotton, and the molecular mechanism of cotton resistance for Verticillium wilt needs to be further investigated. Here, we revealed that the cotton genome contains nine types of GST genes. An evolutionary analysis showed that a newly identified cluster (including Gh_A09G1508, Gh_A09G1509 and Gh_A09G1510) located on chromosome 09 of the A-subgenome was under positive selection pressure during the formation of an allotetraploid. Transcriptome analysis showed that this cluster participates in Verticillium wilt resistance. Because the Gh_A09G1509 gene showed the greatest differential expression in the resistant cultivar under V. dahliae stress, we overexpressed this gene in tobacco and found that its overexpression resulted in enhanced Verticillium wilt resistance. Suppression of the gene cluster via virus-induced gene silencing made cotton plants of the resistant cultivar Nongda601 significantly susceptible. These results demonstrated that the GST cluster played an important role in Verticillium wilt resistance. Further investigation showed that the encoded enzymes of the cluster were essential for the delicate equilibrium between the production and scavenging of H2 O2 during V. dahliae stress.

Pure total flavonoids from Citrus paradisi Macfad induce leukemia cell apoptosis in vitro.

OBJECTIVE: To investigate the potential effect of pure total flavonoids from Citrus paradisi Macfad peel (PTFC) on the proliferation of human myeloid leukemia cells Kasumi-1, HL-60 and K562, and the underlying mechanisms. METHODS: PTFC was extracted from Citrus paradisi Macfad peel and was identified by high performance liquid chromatography. The effect of PTFC on the proliferation and apoptosis of leukemia cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, fluorescent microscopy and flow cytometry, respectively. The effect of PTFC on the expression levels of apoptosis-related regulators was determined by Western blot assay. RESULTS: Treatment with PTFC inhibited leukemia cell proliferation in a dose- and time-dependent manner and triggered Kasumi-1 cell apoptosis. Treatment with PTFC significantly increased the levels of activated poly adenosine diphosphate-ribosepolymerase and caspase-3/-9, but reduced the levels of Mcl-1 expression in Kasumi-1 cells. However, PTFC did not obviously induce HL-60 cell apoptosis. CONCLUSION: PTFC inhibited leukemia cell proliferation and induced their apoptosis by modulating apoptosisrelated regulator expression in leukemia cells in vitro.

Pure total flavonoids from Citrus paradisi Macfadyen act synergistically with arsenic trioxide in inducing apoptosis of Kasumi-1 leukemia cells in vitro.

To investigate the potential effects of pure total flavonoid compounds (PTFCs) from Citrus paradisi Macfadyen separately or combined with arsenic trioxide on the proliferation of human myeloid leukemia cells and the mechanisms underlying the action of PTFCs. The effects of PTFCs separately or combined with arsenic trioxide on the proliferation and apoptosis of leukemia cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), fluorescence microscopy, and flow cytometry. Their effects on the expression levels of apoptosis-related regulators were determined by Western blot assay. PTFCs combined with arsenic trioxide significantly inhibited the growth of Kasumi-1 cells, and apoptosis was confirmed by flow cytometry analysis. Hoechst 33258 staining showed more significant morphological changes and more apoptosis following the combined treatment. Western blots showed changes in the expression of genes for poly ADP-ribose polymerase (PARP), caspase 3/9, and P65. The results indicated that PTFCs separately or combined with arsenic trioxide inhibited proliferation of leukemia cells in vitro and induced their apoptosis by modulating the expression of apoptosis-related regulator genes.

[Analysis of clinical features of traditional Chinese medicine symptoms and syndromes of 220 patients with chronic aplastic anemia].

OBJECTIVE: To study Chinese medicine (CM) syndrome types of chronic aplastic anemia (CAA) patients and the distribution laws of typical CM symptoms in different genders. METHODS: From June 2002 to June 2012, 220 CAA outpatients/inpatients at Department of Hematology, Zhejiang Chinese Medical Hospital were recruited. Patients' symptoms and signs, as well as four diagnostic information at the first onset were collected. CM syndrome differentiation was performed. The syndrome types and typical symptoms were analyzed. RESULTS: (1) In the 220 CAA patients, there were 121 cases of Shen yang deficiency syndrome (55.0%), 18 of Shen yin deficiency syndrome type (8.18%), 81 cases of Shen yin-yang deficiency syndrome (36.82%). (2) The distribution of typical symptoms: fatigue and shortness of breath (77.12% males and 73.53% females), pale complexion (64.41% males and 57.84% females), low temperature of four limbs (12.71% males and 26.47% females), spontaneous perspiration and night sweating (32.20% males and 26.47% females), dry mouth and throat (6.78% males and 6.86% females), feverish feelings in palms and soles (14.41% males and 20.59% females), loose stool (6.78% males and 2.94% females), petechiae and ecchymosis (42.37% males and 43.14% females). CONCLUSIONS: Shen yang deficiency syndrome was most often seen in CAA patients at the initial diagnosis, followed by Shen yin-yang deficiency syndrome. Shen yin deficiency syndrome was the least seen. In CM symptoms, fatigue and shortness of breath were most common seen, followed by pale complexion, skin petechia and ecchymosis.

Transcriptome profiling of Gossypium barbadense inoculated with Verticillium dahliae provides a resource for cotton improvement.

BACKGROUND: Verticillium wilt, caused by the fungal pathogen Verticillium dahliae, is the most severe disease in cotton (Gossypium spp.), causing great lint losses worldwide. Disease management could be achieved in the field if genetically improved, resistant plants were used. However, the interaction between V. dahliae and cotton is a complicated process, and its molecular mechanism remains obscure. To understand better the defense response to this pathogen as a means for obtaining more tolerant cultivars, we monitored the transcriptome profiles of roots from resistant plants of G. barbadense cv. Pima90-53 that were challenged with V. dahliae. RESULTS: In all, 46,192 high-quality expressed sequence tags (ESTs) were generated from a full-length cDNA library of G. barbadense. They were clustered and assembled into 23126 unigenes that comprised 2661 contigs and 20465 singletons. Those unigenes were assigned Gene Ontology terms and mapped to 289 KEGG pathways. A total of 3027 unigenes were found to be homologous to known defense-related genes in other plants. They were assigned to the functional classification of plant-pathogen interactions, including disease defenses and signal transduction. The branch of "SA→NPR1→TGA→PR-1→Disease resistance" was first discovered in the interaction of cotton-V. dahliae, indicating that this wilt process includes both biotrophic and necrotrophic stages. In all, 4936 genes coding for putative transcription factors (TF) were identified in our library. The most abundant TF family was the NAC group (527), followed by G2-like (440), MYB (372), BHLH (331), bZIP (271) ERF, C3H, and WRKY. We also analyzed the expression of genes involved in pathogen-associated molecular pattern (PAMP) recognition, the activation of effector-triggered immunity, TFs, and hormone biosynthesis, as well as genes that are pathogenesis-related, or have roles in signaling/regulatory functions and cell wall modification. Their differential expression patterns were compared among mock-/inoculated- and resistant/susceptible cotton. Our results suggest that the cotton defense response has significant transcriptional complexity and that large accumulations of defense-related transcripts may contribute to V. dahliae resistance in cotton. Therefore, these data provide a resource for cotton improvement through molecular breeding approaches. CONCLUSIONS: This study generated a substantial amount of cotton transcript sequences that are related to defense responses against V. dahliae. These genomics resources and knowledge of important related genes contribute to our understanding of host-pathogen interactions and the defense mechanisms utilized by G. barbadense, a non-model plant system. These tools can be applied in establishing a modern breeding program that uses marker-assisted selections and oligonucleotide arrays to identify candidate genes that can be linked to valuable agronomic traits in cotton, including disease resistance.

[Apoptosis of multiple myeloid cells induced by polysaccharides extracts from Hedyotis diffusa and its mechanism].

OBJECTIVE: To explore the proliferation inhibition and apoptosis effects of polysaccharides extracts from Hedyotis diffusa (PEHD) on multiple myeloma (MM) cell line RPMI 8226 cells in vitro, so as to provide experimental theory for the clinical application in the treatment of MM. METHODS: MTT assay was used to examine the effects of PEHD on cell growth. The apoptotic cells were analyzed by flow cytometry with AnnexinⅤ/PI staining. Hoechst staining was used to observe the morphological changes of RPMI 8226 cell apoptosis. The expression levels of caspase-3,-8,-9, PARP, nucleoprotein NF-κB protein and other channel protein were assayed by Western blotting method. RESULTS: The growth of RPMI 8226 cells were suppressed after treatment with PEHD, the highest inhibition rate reached to 92.3%, the results in the doses from 1 to 4 mg/ml showed a dose-and-time-dependent manner. The proportion of apoptotic cells in 1, 2 and 3 mg/ml PEHD treatment groups for 24 h were 22.52%, 62.31% and 69.94%, respectively, and significantly higher than that of control 8.93%. After treated with PEHD, apoptotic body appeared in RPMI 8226 cells nucleus and the number of apoptotic body increased in a dose-dependent manner. With the increasing of PEHD concentration, the expression of caspase-8,-9,-3 and PARP protein increased. The expression of Mcl-1, Bcl-xl, Bid and Bim protein decreased gradually, but the expression of Bax, Bak and Bad protein increased, and the expression of p-AKT protein (60 kDa) and NF-κB obviously decreased. CONCLUSION: PEHD could inhibited the growth of RPMI 8226 cells and displayed a dose-and-time-dependent manner, its mechanism may involve cell apoptosis induction, which was associated with the activation of caspase-8, caspase-9, and caspase-3 protein and the down-regulation of p-AKT and NF-κB protein expression.

Two new prenylated isoflavones from Sedum aizoon L.

Investigation of a methanol extract from the Chinese endemic species Sedum aizoon L. led to the isolation of two new isoflavone derivatives that were named sedacin A and B (1 and 2). Their structures were elucidated by the basis of spectroscopic analysis. Two new isoflavone derivatives were isolated compounds were assayed for antioxidant activity.

[Responses and corresponding physiological mechanisms of different wheat varieties in their nitrogen efficiency and nitrogen uptake to nitrogen supply].

In this paper, the biological traits, physiological parameters, and enzyme activities related to N assimilation and metabolism of wheat varieties with different nitrogen (N) efficiency were studied under low and high N supply. The results showed that under low N supply, the dry mass of root, leaf, and stem as well as the accumulated N amount in plant were in the order of high N efficiency variety > mid N efficiency variety > low N efficiency variety. The variety with high N uptake efficiency (Ji 97-6360) under low N supply had the highest root active absorption area and TTC-reductive activity and the highest leaf nitrate reductase activity and NO3- content, while the variety with high N physiological efficiency (Shixin 5418) had higher nitrite reductase and glutamine synthetase activities but lower NO3- content and NR activity in its leaf. There was a significant positive correlation between nitrogen use efficiency (NUE) and nitrogen uptake index (NUI) under low N supply. The biological traits, physiological parameters, and enzyme activities related to nitrogen assimilation and metabolism of test wheat varieties were not always the same under high and low N supply.